Cerebral palsy has a complex and multifactorial etiology. Approximately 5%-10% of cases can be ascribed to perinatal hypoxia, but the vast majority of cases are caused by the interplay of several risk factors and antenatal, perinatal, and neonatal events. The strongest risk factors include prematurity and low birth weight. The prevalence of cerebral palsy has remained constant despite improvements in obstetric and neonatal care. For a long time, the only causal factors explored to account for risk for cerebral palsy were complications of labor and delivery. As other periods have been investigated, new associations have come to light. The current understanding of contributors to the risk for cerebral palsy is still incomplete. Multiple causes may interact by way of excitotoxic, oxidative, or other converging pathophysiologic pathways. A single factor, unless present to an overwhelming degree, often may be insufficient to produce cerebral damage, whereas two or three interacting pathogenic assaults may overwhelm natural defenses and produce irreversible brain injury. The low prevalence of cerebral palsy makes the formal testing of preventative strategies difficult. There is a need for such strategies to be carefully assessed in well designed, multicenter, randomized, controlled trials before becoming part of clinical practice, however, so that the balance between harm and benefit is known in advance.